- Drugs given to treat cancer (chemotherapy) can weaken the human immune system. But it can also become weaker because of aging. Interleukin (IL)-7, a molecule produced naturally in the body, can help improve the function of the immune system. Researchers want to study the effects of IL-7 on immune system function in two different groups of older people. One group will be people who have recently completed chemotherapy treatment for breast, colon, or bladder cancer. The other group will be people who have never received chemotherapy.

Objectives:

- To evaluate the effect of IL-7 on the immune system response in older people who either have a normal immune system or have a weakened immune system following chemotherapy.

Eligibility:

People at least 60 years of age who have recently finished chemotherapy for breast, colon, or bladder cancer.

People at least 60 years of age who have never had chemotherapy (control group).

Design:

People in the study will be screened with a physical examination, medical history, and blood tests. Those who have cancer may have other screening tests, such as tumor imaging.

Everyone will receive a series of seven different vaccines commonly used to prevent diseases. We will compare the responses of people in the control group (who have a normal immune system and who will not receive any IL-7) with the responses the people who received the same vaccines with IL-7.

The vaccines will be given randomly in two groups at different times.

Group 1: diphtheria and tetanus, polio, and pneumonia (with two booster shots)

Group 2: hepatitis A (with one booster shot), hepatitis B (with two booster shots), influenza, and PhiX174 (a control vaccine used to test general immune response).

People who have had chemotherapy will also receive three weekly injections of an IL-7 drug. These injections will start 4 weeks after the first group of vaccines. The other group of vaccines will then be given 2 days after the last weekly injection. After each injection of IL-7, participants will provide blood samples for research and monitoring purposes.

Those in the control group will also provide regular blood samples for monitoring and research purposes.

Tetanus Vaccine will be administered according to the random schedule per protocol.

Biological: Polio Vaccine

Polio Vaccine will be administered according to the randomized schedule per protocol.

Biological: Pneumaococcal Vaccine

Pneumaococcal Vaccine will be administered according to the randomization schedule per protocol.

Biological: Hepatitis A Vaccine

Hepatitus A Vaccine will be administered according to the randomization schedule per protocol.

Biological: Hepatitis B Vaccine

Hapatitis A vaccine will be administered according to the randomization schedule per protocol.

Biological: PhiX 174

PHiX 174 Vaccine will be administered according to the rand schedule per protocol.

Detailed Description:

BACKGROUND:

Interleukin-7 is a homeostatic cytokine with a critical role in lymphoid homeostasis through which it exerts its immune-restorative effects, particularly re-expansion of the naive and memory T cell subsets.

The clinical implications of the kinetics, nature and extent of immune reconstitution defect following standard or ablative chemotherapy in older adults with cancer (in particular the lack of reconstitution of large pools naive T cell with broad repertoire diversity and of memory T cells) are not fully appreciated.

As chemotherapy often induces only temporary complete or partial disease responses but no cure, candidates for novel immunotherapy strategies may be significantly impeded in their responses to active immunotherapy attempts, the therapeutic potential of which may be misjudged or altogether overlooked.

rhIL-7 may play a role in immune reconstitution and immune enhancement in various circumstances of immune insufficiency in older individuals following chemotherapy or in the context of enhancing cancer immunotherapy or during immune senescence.

OBJECTIVES:

Determine whether the use of glyco-rhIL-7 impacts the overall immune response to a set of 6 vaccines to be given to patients with cancer.

Evaluate and quantify the impact of glyco-rhIL-7 therapy on specific immune responses to each vaccine (in particular to neo antigens) in older subjects following chemotherapy.

Compare the vaccine responses in the groups where the vaccines are given before or after glyco-rhIL-7 in cancer patients to those in a third group of age matched healthy volunteers not receiving glyco-rhIL-7.

Evaluate the effects of glyco-rhIL-7 therapy on passive memory immune responses (i.e. when not re-stimulated with in vivo recall antigen).

Evaluate and quantify the impact of glyco-rhIL-7 therapy on the T cell receptor diversity in older subjects following chemotherapy.

Evaluate the effects of glyco-rhIL-7 therapy on the quality of T cell specific responses by multiparameter flow cytometry.

Based on the first two primary objectives, consider and discuss the need for larger studies to evaluate the potential benefit of glyco-rhIL-7 administration in a broad, mass protection strategy for an aging population.

CBC with differential, Electrolytes, BUN and Creatinine, Liver panel, mineral panel, all within normal limits for age or, at most, a CTCAE 4.0 grade 1 abnormality,

Absolute Neutrophil Count greater than l000 / mm(3).

Platelet count greater than 75K.

Karnofsky performance status greater or equal to 70%.

Subjects with chronic but adequately treated and stable medical conditions (such as stable hypertension, hyperlipidemia, diabetes, hypothyroidism, etc) may be eligible (PI discretion): stable medical condition defined as no hospitalization, no new diagnoses and no significant adjustment of medications in the 3 months preceding enrollment.

EXCLUSION CRITERIA FOR ALL PARTICIPANTS:

Subjects with significant heart disease defined as:

Significant coronary arterial disease

myocardial infarction in the last 6 months, angina in the previous 3 months,

Troponin elevation at level of myocardial infarction as defined by the manufacturer

Ischemic changes on ECG

Atrio-ventricular block greater than 1st degree, in absence of pacemaker,

QTc greater than 480ms (CTCAE 4.0 grade 1 abnormality is acceptable),

History of ventricular arrhythmia,

Left Ventricular Ejection Fraction below the institutional limit of normal,

Subjects with a history of allergy to influenza vaccine may still participate in the study but will not receive the influenza vaccine,

Inability to give informed consent.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01339000